Breast cancer (BrCa) is one of the most prevalent cancer types and second leading cause of cancer death among Australian women. Mutation in the tumour suppressor p53 in breast cancer correlates with the worst prognosis and high probability of relapse and is seen in 50% of the cases. However, the frequency of mutations varies among the different subtypes. For example, in luminal breast cancer 26% are mutated while 54% in triple negative BrCa. Beside direct mutations in p53, its function or expression is compromised in cancer by deregulation of its key regulators, MDM2, its E3 ligase, and MDMX, a major negative regulator of its activities. MDMX also facilitates MDM2 mediated degradation of p53. Since p53 is not mutated in the majority of luminal BrCa, we hypothesized that either MDM2 or MDMX are deregulated in this cancer subtype. A screen of BrCa samples using tissue microarray had revealed that MDMX is frequently overexpressed in luminal BrCas. We therefore tested the role of MDMX in the suppression of p53 in luminal BrCa expressing wild type p53. We have identified that knock down (KD) of MDMX in MCF-7 (wild type p53) cell line impedes growth in vitro and in vivo. The growth inhibition was shown to be associated with cellular senescence rather than cell death. Surprisingly we found that KD of MDMX also restricted the growth of a breast cancer cell line expressing mutant p53. We hypothesize that MDMX may contribute to BrCa through p53 dependent and independent mechanisms.